Pathological state detection using dynamically determined body index range values

ABSTRACT

We report method of detecting a pathological body state of a patient, comprising receiving a body signal of the patient; determining a body index from said body signal; determining an activity level of said patient; determining a value range for said body index for said patient, based at least in part on said activity level; comparing said body index to said value range; and detecting a pathological state when said body index is outside said value range. We also report a medical device system configured to implement the method. We also report a non-transitory computer readable program storage unit encoded with instructions that, when executed by a computer, perform the method.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims priority to and is a Continuation ofco-pending U.S. patent application Ser. No. 14/084,513, filed on Nov.19, 2013, which claims priority to U.S. Provisional Patent ApplicationSer. No. 61/785,429, filed on Mar. 14, 2013. All of the above-referencepatent applications are hereby incorporated by reference in theirentirety.

FIELD OF THE INVENTION

This disclosure relates to medical device systems and methods capable ofdetecting a pathological body state of a patient, which may includeepileptic seizures, and responding to the same.

SUMMARY OF THE INVENTION

In some embodiments, the present disclosure relates to a method ofdetecting a pathological body state of a patient, comprising receiving abody signal of the patient; determining a first body index from saidbody signal; determining an activity level of said patient; determininga non-pathological range for said first body index, based at least inpart on said activity level; comparing said first body index to saidnon-pathological range for said first body index; and detecting apathological body state when said body index is outside saidnon-pathological range.

In some embodiments, the present disclosure relates to a method ofdetermining a pathological state in a patient, comprising receiving datarelating to an activity level of said patient; determining an activitylevel of the patient based on said data relating to an activity level;receiving at least one body signal of the patient; determining at leasta first body index based on said at least one body signal; dynamicallydetermining a non-pathological range for said at least a first bodyindex based on said activity level; determining that the patient is inone of a non-pathological state and a pathological state, wherein saidpatient is determined to be in a non-pathological state if the at leasta first body index is within said non-pathological range, and saidpatient is determined to be in a pathological state if the at least afirst body index is outside said non-pathological range or isincommensurate for said patient with said activity type and level; andtaking at least one further action based on determining that the patientis in a pathological state, wherein said further action is selected fromtreating said pathological state, issuing a warning to the patient or acaregiver regarding said pathological state, logging the occurrence ofsaid pathological state, or logging a severity of said pathologicalstate.

In other embodiments, the present disclosure relates to a medical devicesystem comprising: at least one kinetic sensor, each said sensorconfigured to collect at least one kinetic signal from a patient; anactivity level module configured to determine an activity level of saidpatient, based at least in part on said at least one kinetic signal; atleast one sensor configured to sense a body signal; a body indexdetermination module configured to determine at least a first body indexbased on said sensed body signal; a body index range module, configuredto determine a non-pathological body index range of said at least afirst body index, based at least in part on said activity type andlevel; and a pathological state determination module, configured todetermine that the patient is in one of a non-pathological state and apathological state, wherein said patient is determined to be in anon-pathological state if the at least a first body index is within saidnon-pathological body index range for said at least a first body index,and said patient is determined to be in a pathological state if the atleast a first body index is outside said non-pathological body indexrange for said at least a first body index.

In other embodiments, the present disclosure relates to a medical devicesystem, comprising at least one metabolic sensor configured to collectat least one metabolic signal relating to an activity level of saidpatient; an activity level module configured to determine an activitylevel of said patient based at least on part on said at least onemetabolic signal; at least one sensor configured to sense a body signal;a body index determination module configured to determine at least onebody index based on said sensed body signal; a body index range module,configured to determine a non-pathological body index range based atleast in part on said activity level; and a module, configured todetermine that the patient is in one of a non-pathological state and apathological state, wherein said patient is determined to be in anon-pathological state if the first body index is within saidnon-pathological body index range, and said patient is determined to bein a pathological state if the first body index is outside saidnon-pathological body index range.

In some embodiments, the activity refers to physical activity (e.g.,body movements), while in other embodiments, activity refers to cerebralactivity (e.g., cognitive, emotional or other brain activity).

In some embodiments, the present disclosure relates to a non-transitorycomputer readable program storage unit encoded with instructions that,when executed by a computer, perform a method as described above.

BRIEF DESCRIPTION OF THE DRAWINGS

The disclosure may be understood by reference to the followingdescription taken in conjunction with the accompanying drawings, inwhich like reference numerals identify like elements, and in which:

FIG. 1 shows a schematic representation of a medical device system,according to some embodiments of the present disclosure;

FIG. 2A shows a schematic representation of a body index range module ofthe medical device system of FIG. 1, according to some embodiments ofthe present disclosure;

FIG. 2B shows a schematic representation of an additional factor moduleof the medical device system of FIG. 1, according to some embodiments ofthe present disclosure;

FIG. 3A shows the dynamic nature of an exemplary non-pathological heartrate range, according to some embodiments of the present disclosure;

FIG. 3B shows the dynamic nature of an exemplary non-pathological heartrate range, according to some embodiments of the present disclosure;

FIG. 4 shows the dynamic nature of an exemplary non-pathological heartrate range in more detail, according to some embodiments of the presentdisclosure;

FIG. 5 shows the dynamic nature of an exemplary non-pathological heartrate range in more detail, according to some embodiments of the presentdisclosure;

FIG. 6 shows a flowchart representation of a method, according to someembodiments of the present disclosure;

FIG. 7 shows a flowchart representation of a method, according to someembodiments of the present disclosure;

FIG. 8 shows a flowchart representation of a method, according to someembodiments of the present disclosure;

FIG. 9 shows a flowchart representation of a method, according to someembodiments of the present disclosure;

FIG. 10 shows a flowchart representation of a method, according to someembodiments of the present disclosure;

FIG. 11 shows a conceptual depiction of pathological andnon-pathological body data (e.g., heart rate) value ranges, according tosome embodiments of the present disclosure;

FIG. 12 shows a flowchart representation of a method, according to someembodiments of the present disclosure.

While the disclosure is susceptible to various modifications andalternative forms, specific embodiments thereof have been shown by wayof example in the drawings and are herein described in detail. It shouldbe understood, however, that the description herein of specificembodiments is not intended to limit the disclosure to the particularforms disclosed, but on the contrary, the intention is to cover allmodifications, equivalents, and alternatives falling within the spiritand scope of the disclosure as defined by the appended claims.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS

Illustrative embodiments of the disclosure are described herein. Forclarity, not all features of an actual implementation are described. Inthe development of any actual embodiment, numerousimplementation-specific decisions must be made to achievedesign-specific goals, which will vary from one implementation toanother. Such a development effort, while possibly complex andtime-consuming, would nevertheless be a routine undertaking for personsof ordinary skill in the art having the benefit of this disclosure.

Embodiments of the present disclosure provide for a medical devicecapable of monitoring an activity type and/or level of a patient anddynamically determining a non-pathological body index range based uponan activity type and/or level of the patient. The dynamically determinedbody index range may be used to classify a body system of the patient asbeing in a pathological or non-pathological state. An activity level ofthe patient may in some embodiments be determined from a kinetic sensorsuch as an accelerometer, while in other embodiments activity level mayrefer to a metabolic activity level as determined from a metabolicsensor measuring, e.g., glucose consumption or blood pH or oxygenconsumption. Kinetic sensors for use in embodiments herein may includeany sensor that measures a kinetic activity of the patient, includingmovement, acceleration, velocity, position, force, or direction plusduration. The classification of body systems of the patient aspathological or non-pathological may further be based on health status,fitness level and prevailing environmental conditions (e.g.,temperature, altitude, humidity, time of day, etc.) or patientcharacteristics (e.g., age, gender, BMI, fitness level, medications).

This invention recognizes that to determine (using body systems andtheir features) whether a body system is functioning pathologically ornon-pathologically with a clinically worthwhile degree of accuracy andreliability, one must take into account the type and/or level ofactivity being performed by a subject at the time thepathological/non-pathological determination is made. For example, if theobjective is to determine if and when a patient is in a seizure statethat manifests with increases in heart rate, it is imperative to knowwhether or not a given increase in heart rate is associated with achange in activity (e.g., physical or emotional) and if such a change inactivity is occurring, to determine if the heart rate increase iscommensurate with said activity type and level. This may be accomplishedby a dynamical adjustment of value ranges of body signal features toavoid false diagnoses.

In some embodiments, a non-pathological range for a body index may bedynamically determined (which may include an adjustment to a previouslydetermined non-pathological body index range) based on the activity typeand/or level of the patient. As used herein, the determination oradjustment may be considered to be “based on” the activity level so longas the determination of the non-pathological range takes intoconsideration the activity level, even though other factors (e.g.,patient-specific or patient environmental factors) may also be used todetermine the non-pathological range. In some embodiments, more than onebody index from at least one body signal may be determined, andcorresponding non-pathological ranges for each of the body indices maybe determined based on the activity type and/or level. Once thenon-pathological body range is determined, a determination of apathological or a non-pathological state of the patient may be made bycomparing the body index to the dynamically determined non-pathologicalbody index range. In particular, the patient may be determined to be ina non-pathological state if the body index is within thenon-pathological body index range, and the patient may be determined tobe in a pathological state if the first body index is outside thenon-pathological body index range. Where multiple body indices andcorresponding non-pathological body ranges are determined, thedetermination of a pathological or non-pathological state may be basedon more than one such index and range. When a detection of apathological state is made, the medical device may perform a responsiveaction, such as providing a therapy, providing a warning, determining aseverity of the pathological state, and/or logging the determination ofthe pathological state. FIG. 1 shows a schematic representation of amedical device system, according to some embodiments of the presentdisclosure. The medical device system 100 may comprise a medical device200, kinetic sensor(s) 212, lead(s) 211 coupling the kinetic sensor(s)212 to the medical device 200, body signal sensors 282 and body signalleads 281 coupling body signal sensors 282 to medical device 200. Themedical device system 100 may be fully or partially implanted, oralternatively may be fully external. In one embodiment, kineticsensor(s) 212 may each be configured to collect at least one signal froma patient relating to an activity level of the patient. For example,each kinetic sensor 212 may be selected from an accelerometer, aninclinometer, a gyroscope, an ergometer, an electromyography (EMG)sensor, a body temperature sensor, an oxygen consumption sensor, alactic acid accumulation sensor, a sweat sensor, a neurogram sensor, aforce transducer, or an ergometer. Brain, metabolic or other sensors maybe used in some embodiments. For example sensors (electrical, thermal,chemical, etc.) may be placed in one more structures (cortex, basalganglia, cortico-spinal tract, cerebellum) involved in motor control todetermine the physical work performed by a person.

Various components of the medical device 200, such as controller 210,processor 215, memory 217, power supply 230, communication unit 240,warning unit 291, therapy unit 292, and logging unit 293 and severityunit 294 have been described in other patent applications assigned toFlint Hills Scientific, LLC or Cyberonics, Inc., such as, U.S. Ser. No.12/770,562, filed Apr. 29, 2010; U.S. Ser. No. 12/771,727, filed Apr.30, 2010; U.S. Ser. No. 12/771,783, filed Apr. 30, 2010; U.S. Ser. No.12/884,051, filed Sep. 16, 2010; U.S. Ser. No. 13/554,367, filed Jul.20, 2012; U.S. Ser. No. 13/554,694, filed Jul. 20, 2012; U.S. Ser. No.13/559,116, filed Jul. 26, 2012; and U.S. Ser. No. 13/598,339, filedAug. 29, 2012; U.S. Ser. No. 12/896,525, filed Oct. 1, 2010, now U.S.Pat. No. 8,337,404, issued Dec. 25, 2012; U.S. Ser. No. 13/098,262,filed Apr. 29, 2011; U.S. Ser. No. 13/288,886, filed Nov. 3, 2011; U.S.Ser. No. 13/554,367, filed Jul. 20, 2012; U.S. Ser. No. 13/554,694,filed Jul. 20, 2012; U.S. Ser. No. 13/559,116, filed Jul. 26, 2012; andU.S. Ser. No. 13/598,339, filed Aug. 29, 2012. Each of the patentapplications identified in this paragraph is hereby incorporated hereinby reference.

The medical device 200 may comprise an activity level module 250,configured to determine an activity type and/or level of the patient,based at least in part on body signal data collected by sensor(s) 212.By “activity level” is meant the level of one or more of the patient'senergy consumption (which may be termed “work level” and mayconveniently be measured by proxies such as body movement, EMG activity,O₂ consumption or heart rate, among others, and from which the classicaldefinition of work is not excluded), emotional activity (e.g., mildversus intense emotion), or cognitive activity (e.g., mild versusintense thinking). In some embodiments, information relating to worklevel may be collected by an accelerometer, etc. described above.

The activity level module 250 may determine an activity level of thepatient at any sampling frequency for kinetic sensors 212. In oneembodiment, the activity level module 250 is configured to determine theactivity level with a sampling frequency ranging from about one thousandtimes per second to about once every four hours. The activity levelmodule 250 may determine an activity level for at least one time windowor may determine an instantaneous measure of activity. The at least onetime window may be on a microscopic time scale (less than 10 min), amesoscopic timescale (10 min-24 hr), or a macroscopic timescale (greaterthan 24 hr). Other temporal scales (smaller or larger) than those listedabove may be applied. The medical device 200 may also comprise a bodyindex range module 260, configured to determine body index ranges of thepatient, based at least in part on the activity level determined by theactivity level module 250. In some embodiments, the body index rangemodule 260 may determine a reference value range for a certain bodyindex (e.g., heart rate). In one embodiment, the body index range module260 may determine a non-pathological range for a particular body indexbased on the activity level determined by the activity level module 250.By comparing an actual body index (e.g., as determined from a body indexby a body index determination module 280) to the reference value range(e.g., a non-pathological range), it is possible to determine whetherthe actual body index is in the non-pathological range or in apathological range. Because of variations in pathological andnon-pathological ranges associated with activity levels, a particularactual body index value may indicate that the patient is in apathological state at one activity level but indicate that the patientis in a non-pathological state at another activity level. Thus, bodyindex range module 260 may determine that the same body index value(e.g., the same heart rate) in the same patient is either pathologicalor non-pathological based on the activity level, activity type, or othervariables (e.g., fitness level). In some embodiments, the body indexrange module 260 may determine both a pathological range value and anon-pathological range value for the one or more body indices. By takinginto account the effects on body indices of activity levels (e.g.,kinetic activity or metabolic activity), non-pathological ranges forparticular indices derived from monitored body signals may bedynamically determined (which includes dynamic adjustment of theindices) so that detection of pathological states may be made with greataccuracy. That is, false negative and false positive detections ofpathological events may be reduced by dynamically determiningpathological or non-pathological ranges for particular body indicesbased on activity type and level or other variables (e.g., environmentalconditions).

In some embodiments, ranges determined by the body index range module260 may be based upon additional factors beside the activity level ofthe patient. For example, determination of a reference value range(e.g., a non-pathological body index range or a pathological body indexrange) may, in addition to the activity level of the patient, be basedon data collected in real-time, and may include patient body data and/orenvironmental conditions that have an influence on the non-pathologicalbody index ranges. These actions may be performed with or without regardto the patient's body systems' status (normal or abnormal), andadjustments may be made to the boundaries of the non-pathological (orpathological) range so that a real-time body index value may, in certainsituations or circumstances, be indicative of a certain pathologicalstate (e.g., epileptic seizure) and in others, not be indicative of thepathological state. In an adult with a resting heart rate of 110 bpm(indicative of cardiac dysfunction) who also suffers from epilepsy,seizures may further elevate the heart rate and said elevation in thecontext of no change in activity type or level, would be indicative ofthe occurrence of an epileptic seizure in said subject. That is, thecollected body data may be a priori, normal or abnormal and if abnormal,the occurrence of a transient/reversible change in the state of a bodysystem may further alter said abnormal activity.

In such embodiments, the additional factor(s) may be determined by anadditional factor module 270 configured to determine one or more of atime of day, an environmental condition, a patient's body weight andheight, a patient's body mass index, a patient's gender, a patient'sage, an indicator of said patient's overall health, or an indicator ofsaid patient's overall fitness, and provide an output relating to theadditional factor determination. The body index range module 260 maythen be configured to determine a non-pathological body index rangebased at least in part on the output of the additional factor module270.

The body index range module 260 may be configured to determine saidreference value range (e.g., non-pathological or pathological body indexrange) based at least in part on a kinetic signal collected from a timewindow ending at the current time. In some embodiments, the body indexrange module 260 may perform calculations based upon a moving timewindow used to collect body signals.

In one embodiment, the body index range module 260 may be configured todetermine a non-pathological range for a first time point based on thepatient's activity in a first time window prior to said first timepoint. The first time window may comprise a time interval ranging from 1second to two hours. In one embodiment, the first time window maycomprise one of: said first time point and the preceding 1 second; saidfirst time point and the preceding 10 seconds; said first time point andthe preceding 30 second; said first time point and the preceding 1minute; said first time point and the preceding 2 minutes; said firsttime point and the preceding 3 minutes; said first time point and thepreceding 5 minutes; said first time point and the preceding 10 minutes;said first time point and the preceding 30 minutes; said first timepoint and the preceding 1 hour; said first time point and the preceding2 hours. In some embodiments, the body index range module 260 may alsouse the patient's historical health information to generate anon-pathological range for one or more body indices. Historical data ofthe patient may provide indications as to expected changes innonpathological ranges of the body index during certain time periods.

The body index range module 260 may make its determination at anysampling frequency. In one embodiment, the body index range module 260is configured to configure to determine a non-pathological body indexrange for a body index (e.g., an instantaneous or average heart rate) atan update frequency ranging from about one thousand times per second toabout once every four hours.

The medical device 200 may further comprise a body index determinationmodule 280, configured to determine one or body indices of the patient.The body index may be heart rate (instantaneous or in a short-term orlong-term time window), heart rate rhythm, heart rate variability, bloodpressure, blood pressure variability, respiratory rate, respiratoryrhythm, respiratory rate variability, end tidal CO₂, kinetic activity,cognitive activity, dermal (including electro-dermal) activity, chemical(including electro-chemical) activity, arterial pH, cortisol level,catecholamine level, or blood oxygen saturation, among others. Forexample, the body index may be heart rate. The body index may bedetermined based on a signal collected from one or more body signalsensor(s) 282, which may be coupled to the medical device 200 by bodysignal lead(s) 281.

The medical device 200 may further comprise a pathological statedetermination module 290, configured to determine an occurrence of apathological state of the patient, in response to the body index beingoutside of a non-pathological or a pathological body index range for thebody index for the prevailing activity type, level and other conditions.An occurrence of any pathological state that may be associated with abody signal outside a non-pathological body index range provided byanalysis of the patient's activity level may be determined by thepathological state occurrence module 290.

In one embodiment, the pathological state is an epileptic event, e.g.,an epileptic seizure. For example, if the body signal is heart rate,then an instantaneous heart rate above the non-pathological heart raterange determined by the body index range module 260 may indicate atachycardia episode frequently seen with epileptic seizures originatingfrom or spreading to certain brain regions, and an instantaneous heartrate below the non-pathological heart rate range may indicate abradycardia episode occasionally seen with epileptic seizuresoriginating from certain brain regions. By taking into account theactivity level of the patient and other conditions, false positiveand/or negative detections of pathological events may be avoided, sincethe effects of high or low activity levels upon heart rate may be usedto adjust (e.g., raise, lower, widen or narrow) non-pathological orpathological heart rate ranges. For example, if the patient is engagedin vigorous exercise, the non-pathological range for heart rate may beincreased and the range may be widened. If the patient is sedentary orsleeping, acceptable non-pathological ranges for heart rate may belowered and narrowed.

FIG. 2A shows a block diagram schematic representation of the body indexrange module 260 in more detail, according to some embodiments of thepresent disclosure. The body index range module 260 may comprise anactivity module 263. The activity module 263 may be configured toprovide a determination of the source(s) of the patient's activitylevel, e.g., whether the sources are kinetic (body movement), emotional,or cognitive activity.

The body index range module 260 may comprise a work level lookup table264. The work level lookup table 264 may provide information relating anon-pathological body index range to an activity level of the patient.In one embodiment, the work level may refer to the metabolic changes inthe patient's body based upon the amount of energy expended by thepatient. However, other measures of work level may be also used,including the classic reference to work level involving amount of forceused, displacement, etc. For example, if the body index is heart rate,an activity level indicative of vigorous aerobic exercise may be relatedto a non-pathological heart rate range of 120-140 BPM.

The body index range module 260 may comprise a work level—patient andenvironmental conditions correlation module 265. The work level—patientand environmental conditions correlation module 265 may perform acorrelation of information from the additional factor module 271 and thework level lookup table 264 to determine a non-pathological body indexrange from the current patient and environmental conditions and currentwork level and source(s) thereof.

The body index range module 260 may further comprise a non-pathologicalbody index range determination module 266. The non-pathological bodyindex range determination module 266 may determine the non-pathologicalbody index range from the patient's activity level for a given worklevel as determined by one or more of activity module 263, work levellookup table 264, or work level—patient and environmental conditionsmodule 265. In some embodiments, the body index range module 260 mayfurther comprise a pathological body index range determination module268, which may determine a pathological body index range from by one ormore of activity module 263, work level lookup table 264, or worklevel—patient and environmental conditions module 265.

FIG. 2B shows a block diagram schematic representation of the additionalfactor module 270 in more detail, according to some embodiments of thepresent disclosure. Additional factor module 270 may comprise a patientand environmental conditions module 271. The patient and environmentalconditions module 271 may be configured to provide a determination ofone or more patient and environmental conditions. For example, thepatient and environmental conditions module 271 may be configured toprovide the time of day, such as by maintaining an internal clock,fetching a clock value from the processor 210, or requesting a time ofday value from an external source via communication unit 240, amongothers. For another example, the patient and environmental conditionsmodule 271 may be configured to provide the ambient temperature or theambient humidity, altitude, such as by requesting the temperature from athermometer, or the humidity from a hygrometer, in contact with ambientair. For additional examples, the patient and environmental conditionsmodule 271 may be configured to provide the patient's body weight, thepatient's BMI, or the patient's fitness level, among other factors.

The additional factor module 270 may comprise a patient andenvironmental conditions lookup table 272. The patient and environmentalconditions lookup table 272 may provide information relating anon-pathological or pathological body index range to patient andenvironmental conditions as determined by module 271. For example, ifthe body index is heart rate, and the environmental condition is thetime of day, a time of day between midnight and 6:00 AM may be relatedto a non-pathological heart rate range of 40-70 BPM, and this relationmay be stored in patient and environmental conditions lookup table 272.

FIG. 3A shows the dynamic relationship between non-pathological patientactivity levels (e.g., as determined from a tri-axial accelerometer) andan exemplary body index (heart rate). The patient's activity level isshown on the x-axis and heart rate (HR) is on the y-axis. Althoughnon-pathological activity level is shown in FIG. 3A as a singlecontinuous parameter, a plurality of discrete activity levels or statesmay also be used to correlate heart rate (or another body index) toactivity levels in some embodiments of the invention. Because heart rateis a non-stationary parameter that may be influenced by many differentfactors in addition to activity levels (e.g., the patient's age, sex,body mass index, fitness level, hydration status, environmentalconditions such as temperature, humidity, etc.) a particular activitylevel may result in a short-term heart rate anywhere within theassociated non-pathological heart rate range.

FIG. 3A shows an activity-based, non-pathological heart rate rangeregion bounded by upper non-pathological HR boundary line 310 and lowernon-pathological HR boundary line 320. Both the upper and lower boundsof the non-ictal heart rate region increase as activity level increases(e.g. from a sleep state to a resting, awake state) and reach theirhighest values for strenuous exertion. In addition, the width of thenon-pathological heart rate ranges narrows as activity levels and heartrates increase, which is consistent with the known reduction in heartrate variability at high levels of exertion. When the patient is in anon-pathological state (e.g., when an epileptic patient is not having aseizure), for a particular activity level the patient's short-term heartrate should fall within a non-pathological heart rate range associatedwith that activity level. Referring to FIG. 3A, at a particular activitylevel A1—corresponding to a sleeping activity level—a non-pathologicalHR range R1 may be determined between upper and lower boundaries 310 and320. Another non-pathological heart rate range R2 may be established byupper and lower boundaries 310 and 320 for resting awake activity levelA2. At activity levels A3 and A4, corresponding to moderate andstrenuous exercise, respectively, corresponding non-pathological HRranges R3 and R4 may be determined from upper boundary 310 and lowerboundary 320. As noted, the width of the non-pathological heart rateranges decrease as activity levels increase, and thus R1>R2>R3>R4.

Referring to FIG. 3B, non-pathological heart rate ranges as a functionof activity level are determined by upper and lower boundaries 330, 350.For a particular activity level A5, the non-pathological range liesbetween heart rate H1 and H2. At heart rates above H1, the patient'sheart rate may be pathologically high (e.g., when the patient is havinga seizure characterized by elevated heart rate), while at heart ratesbelow H2, the patient's heart rate may be pathologically low (e.g., whenthe patient is having a seizure characterized by reduced heart rate).

Upper and lower non-pathological heart rate boundaries 330, 350 may bedetermined from patient population data and stored in a memory of animplantable or body-worn medical device. When needed, the heart ratedata may be retrieved from the memory for use by the medical device todetermine whether the patient's heart rate is within a non-pathologicalrange appropriate in view of the patient's activity level.Alternatively, heart rate ranges may be determined by calculation from aformula based on the patient's activity level, which may optionally takeinto account one or more additional factors such as those previouslymentioned.

Upper and lower boundaries 330, 350 may alternatively be determinedempirically from patient-specific data collected over time for a varietyof activity levels. For example, the patient may be subjected to one ormore stress tests such as a walking test on a treadmill, with heartrates determined at each of a variety of different activity levels(e.g., as determined from one or more of a three-dimensionalaccelerometer, an electromyogram, gyroscope, and/or imaging devices suchas a camera). Other activity level tests may be performed to determineupper and lower boundaries 330, 350. In one embodiment, uppernon-pathological boundary 330 may be determined as an upper percentilevalue (e.g., the 90^(th), 95^(th), or 99^(th) percentile) of thenon-pathological heart rates measured at times corresponding to theparticular activity level. Thus, a linear or higher-order polynomial maybe fitted through the target upper percentile values over a range ofactivity levels to obtain the upper boundary 330. Similarly, anotherpolynomial may be fitted through a target percentile value (e.g.,5^(th), 2^(nd), 1^(st))) to obtain the lower boundary 350.

Additional curves may be determined by fitting polynomials to additionaltarget percentile values of the activity level/HR data. Referring againto FIG. 3B, a median boundary line 340 may be determined by fitting apolynomial through the 50^(th) percentile values over the range ofactivity levels. Additional percentile values may be determinedsimilarly. In addition, the overall range may be further divided intosub-ranges (e.g., first, second, third and fourth quartile ranges).

In some embodiments of the present invention, upper and lower boundariesmay be determined for one or more specific types of pathological states.For example, separate upper and lower heart rate boundaries as afunction of activity level may be determined for simple partialseizures, complex partial seizures, or generalized tonic-clonicseizures, among others. Without being bound by theory, these upper andlower boundaries for each seizure type may be determined as specificpercentile value curves from those described immediately above. Forexample, in one embodiment a non-pathological boundary for a simplepartial seizure may be determined as a 90^(th) percentile value for aparticular activity level, while a non-pathological boundary for acomplex partial seizure may be determined as a 95^(th) percentile valuefor a particular activity level.

In some embodiments, upper and lower boundaries for simple partial andcomplex partial seizures may be determined by activity levels and theresults of an awareness test. Where the awareness test indicates thatthe patient has not lost awareness, the heart rates measured while thepatient remains aware may be used (along with activity levels) as datato determine upper and lower heart rate boundaries for simple partialseizures. When and if the patient loses awareness, the data of heartrate and activity level may be used to determine upper and loweractivity level heart rate boundaries for seizures associated with lossof function, such as complex partial, complex partial with secondarygeneralization, or generalized seizures.

FIGS. 3A and 3B together show that a non-pathological heart rate (orother body index) range may be established for a given activity level ofthe patient. In some embodiments, the range may be a unique range basedon historical data for the patient, while in other embodiments data forpatient populations may be used, at least until patient-specific datacan be obtained. For simplicity, FIGS. 3A and 3B depict the upper andlower boundaries as being linear. It will be appreciated, however, thatthe boundaries for an actual patient would not necessarily be linear,particularly where additional factors may be considered.

The dynamic relationship between non-pathological heart rates andactivity levels may be exploited to detect pathological states such asepileptic seizures by determining when the patient's heart rate isincommensurate with the patient's activity level. By monitoring thepatient's activity level and heart rate, it is possible to determinewhen the patient's heart rate falls outside the non-pathological rangesas the patient's activity levels change over time. FIG. 4 shows thepatient's heart rate and the dynamically changing non-pathological heartrate range as the patient's activity levels change over time, with timeshown on the x-axis and heart rate (HR) and non-pathological heart raterange shown on the Y-axis. As patient activity levels change over thecourse of time (e.g., over the course of a day), commensuratenon-pathological HR ranges may be determined and utilized to detect theonset of pathological states. A non-pathological range A provides arelatively low range that may correspond to sleeping or resting. Aslightly higher (and narrower) range B may correspond to higher activitylevels of the patient, and a significantly higher (but narrower still)range C may correspond to an exercise period, which returns to a lower(and broader) range D after the patient stops exercising.

FIG. 4 indicates that the width of a non-pathological body index rangemay change based on activity levels, optionally in view of additionalfactors as discussed above. For example, at points A and D, the rangemay relatively broad, reflecting relatively low activity levels. Incontrast, at point C, corresponding to strenuous exercise, the range maybe relatively narrow, arising from the patient's heart rate approachinghis or her maximum heart rate. Periods of elevated heart rate due toexertion may be highly correlated with activity level as measured by,e.g., an accelerometer. FIG. 5 shows the dynamic nature of heart ratechanges, along with exemplary thresholds for the global maxima 550,global minima 560, ictal maxima 570 and ictal minima 580 for aparticular patient. Heart rate changes associated with an exertionalactivity are shown by line 530, and for a cycle of waking and sleepingby line 540. During the exertional activity 530, which may occur over atime range from 5 minutes to an hour, the patient's heart rate risesfrom a non-exertional waking level W to global maxima 550 correspondingthe patient's maximum heart rate, and then returns to a baselinenon-exertional heart rate W. Global maximum 550 may be reached, forexample, during an extended period of vigorous/strenuous exertion orduring pathological states. By comparison, a relatively sedentary cycle540 may take place over a longer time frame, e.g., 1-2 days, and mayshow a much narrower heart rate ranging from the global minima 560 towaking non-exertional rate W.

FIG. 5 also shows that the exertional heart rate may reach (or exceed)ictal minima 550 and ictal maxima 560 heart rates corresponding tominimum and maximum heart rate values associated with seizures. Thus,FIGS. 3 and 5 show that heart rate alone is insufficient to accuratelydistinguish pathological and non-pathological states, at least for someactivity levels. For lower activity levels, however, the expected heartrate values shown in line 540 may be sufficient to distinguish seizuresfrom non-seizures, if the lower activity level is considered. Thus, fora low activity level as represented by line 540, an expectednon-pathological range may be bounded on the low side by the globalminima 560, and on the upper side by a rate slightly higher than normalwaking rate W, e.g., W+10 bpm. The upper and lower boundaries may varybased on the activity level. Thus, as activity levels rise, both theupper and lower levels of the expected range may be elevated as afunction of the activity level and possibly other factors such as thepatient's fitness level, age, sex, etc. The less the difference betweenthe ictal minima 550 and the global minima 560, the lower thespecificity of detection and the higher the number of false positives.As the activity level increases such that the upper boundary nears theictal maxima and minima range, the accuracy of distinguishing seizuresfrom non-seizure states may be further diminished if heart rate andactivity type/level are the only variables used for pathological statedetection purposes. However, by considering additional factors such asthe patient's fitness level, age, environmental conditions, etc.,accuracy levels may be maintained until activity levels result in bodyindex/indices changes that lie within the range bounded by ictal maxima570 and ictal minima 580. The degree of overlap between physiologicalexertional and either pathological exertional or non-exertional (e.g.central neurogenic) changes in body index values is largely dependent onthe body index. For example, while heart change increases between acomplex partial seizure and a certain exercise activity may beindistinguishable, arterial pH and gases are much less susceptible tochanges under physiologic conditions and therefore more specificindicators (than heart rate) of the onset of pathological states.

Although FIGS. 3-5 are directed to heart rate and a non-ictal range,analogous non-pathological ranges may be determined for heart ratevariability, blood pressure, respiratory rate, dermal activity, oroxygen saturation, among others. As with heart rate, such other bodyindices may also be expected to vary with time of day, activity level,or other parameters. Also, disorders other than epilepsy would beexpected to have non-pathological ranges of one or more of these bodyindices.

FIG. 6 shows a flowchart representation of a method 600, according tosome embodiments of the present disclosure. The method 600 may comprisereceiving activity level data at 610. The method 600 may, in someembodiments, also comprise receiving at 620 data related to one or morepatient or environmental conditions.

The method 600 may comprise dynamically adjusting at 630 anon-pathological body index range based upon at least on activity leveldata, and optionally based on the patient or environmental conditions.In some embodiments, the non-pathological body index range may beadjusted by updating either or both of the lower or upper bounds of therange, or selecting the range from a lookup table or bank of ranges.

The method also comprises receiving body data and determining one ormore body indices at 635. The one or more body indices correspond to theindices for which non-pathological (or pathological) ranges have beendetermined at 630. The body indices may be compared at 640 to thedynamically adjusted non-pathological (or pathological) body indexranges. If the patient is found at 650 to be in a pathological state,e.g., if the patient's body index is outside the non-pathological bodyindex range (or if the reference pathological values are incommensuratefor the activity type, level and/or other conditions), the method 600may comprise at least one further action taken at 670, e.g., treatingthe pathological state, issuing a warning to the patient or a caregiverregarding the pathological state, logging the occurrence and/or theseverity of the pathological state, etc. In one embodiment, the severitymay be measured by a magnitude and/or duration of a pathological statesuch as a seizure, a type of autonomic change associated with thepathological state (e.g., changes in heart rate, breathing rate, brainelectrical activity, the emergence of one or more cardiac arrhythmias,etc.). If the patient is found at 650 to not be in a pathological state,the method 600 may comprise continued monitoring of the patient at 660.In either event, after the further action(s) taken at 670 or thecontinued monitoring at 660, flow may return to receiving activity leveldata at 610.

FIG. 7 shows a flowchart representation of a method 700 of dynamicallyadjusting a non-pathological range for at least one body index rangeaccording to one embodiment of the invention. The non-pathological rangefor the at least one body index may be based upon work level data andpatient or environmental conditions, according to some embodiments.First, patient activity data may be received at 710. This received datamay be related to the origin(s), type, or magnitude of the activity,i.e., may provide a qualitative, semi-quantitative, or quantitativemeasure of the kinetic, emotional, and/or cognitive contributions to thepatient's activity level. A non-pathological range (e.g., a non-ictalheart rate range) for the at least one body index may be determined at720, based on the patient's activity. In some embodiments of theinvention, the non-pathological range for the at least one body indexmay be adjusted in view of at least one patient or environmentalcondition. In such cases, patient or environmental condition data may bereceived at 730. The activity-based non-pathological range for the atleast one body index from 720 may then be adjusted at 740 (e.g., basedon a lookup table or calculations). The magnitude of the adjustment tothe activity-based range may depend upon the sensitivity of theparticular body index to the patient or environmental factor(s) beingconsidered. Body data of the patient may be received, and a change inthe at least one body index may be determined, at 750.

From the non-pathological body index range(s) and the at least one bodyindex corresponding thereto, it may be determined at 760 whether thechange in the at least one body index is commensurate with the patient'sactivity level or type, and (in some embodiments) the at least onepatient or environmental condition(s). If the change is commensuratewith the activity level and conditions, then the non-pathological bodyindex range (e.g., a non-ictal heart rate range) is not adjusted at 770based on activity level or the patient or environmental condition(s),and flow returns to 710. If the change is not commensurate with thepatient's activity level or type, or with patient/environmentalcondition(s), then the non-pathological body index range (e.g., anon-ictal heart rate range) is adjusted at 780 based on activity level,and an action is taken at 790.

It should be noted that, in some embodiments, adjustments at 740 of thenon-pathological body index range may be required only in situationswhere pathological and non-pathological values of the body signaloverlap.

FIG. 8 shows a flowchart representation of a method 800 of determiningif the patient is in a pathological or a non-pathological state. First,an activity level of the patient may be determined at 810, and anon-pathological body index range may be determined at 820, based atleast in part on the activity level. In some embodiments, one or moreadditional factors may be determined at 830 and the non-pathologicalbody index (BI) range may be determined at 820, based at least in parton the additional factor(s) and/or the activity level. Examples of suchadditional factors include, but are not limited to, those describedsupra.

After the non-pathological body index range is determined at 820, a bodyindex value of the patient may be determined at 840. In someembodiments, multiple body indices may be determined, to increase thespecificity and sensitivity of distinguishing between pathological andnon-pathological states. If the body index value is determined at 850 tobe outside the non-pathological body index range, then it may bedetermined at 860 that a pathological state of the patient has occurred.Thereafter, a further action, such as warning, treating, or logging theoccurrence and/or the severity of the pathological state, may be takenat 870. If the body index value is found at 850 to be within thenon-pathological body index range, then flow may return to any ofdetermining the body index value at 840, determining thenon-pathological body index range at 820, or determining the activitylevel at 810.

FIG. 9 shows a flowchart representation of a method 900, according tosome embodiments of the present disclosure. One or more body signals,such as autonomic, metabolic, endocrine, or tissue stress signals, maybe received at 910 and, in some embodiments, the body signals from afirst time window may be buffered at 915. The body signals buffered at915 may be the same or different from the first body signal referred tobelow.

A determination is made at 920 whether the value of the first bodysignal has changed. If the body signal is unchanged (i.e., is the sameor has only insubstantial differences to prior value(s)), then flowreturns to receiving at 910. If the body signal has changed, it is thendetermined at 930 whether a change in the patient's activity level,e.g., work load, kinetic activity, cognitive activity, or emotionalactivity has occurred.

If the determination at 930 is that the patient's activity level isunchanged, then one or more actions may be taken at 940, such as issuinga pathological state (e.g., an epileptic seizure) detection, issuing awarning of the pathological state, delivering a therapy for thepathological state to the patient, or logging the pathological state orthe severity thereof. If the patient's activity level has changed, thenanalysis of the body signals, if any, buffered at 915 may begin (element950).

The analysis at 950 may indicate whether there is a change in one ormore buffered body signals other than the first body signal. If it isdetermined at 960 that no change has occurred in other body signals thatshould change with the pathological state, then any previously takenaction, such as issuing a pathological state detection, issuing awarning of the pathological state, delivering a therapy for thepathological state to the patient, or logging the pathological state orthe severity thereof, may have been taken in error. In light thereof,the detection, the warning, etc., may be canceled, etc. at 970 and thisinformation logged for future reference.

FIG. 10 shows a flowchart representation of a method 1000, according tosome embodiments of the present disclosure. One or more body signals,such as autonomic, metabolic, endocrine, or tissue stress signals, maybe received at 1010. A determination may be made at 1020 whether thevalue of a first body signal has changed. If said body signal isunchanged (i.e., is the same or has only insubstantial differences toprior value(s)), then flow returns to receiving at 1010.

If the value of the first body signal has changed, then it may bedetermined whether the value has decreased (at 1030) or increased (at1040). If both element 1030 and element 1040 indicate the value hasneither decreased nor increased, then flow may return to receiving at1010. If one or the other of elements 1040 and 1030 indicate the valuehas increased or decreased, then a determination may be made at 1050 or1060 whether the increase or decrease is commensurate with the patient'sactivity level or a change thereof.

From either determination at 1050 or 1060, if the change is commensuratewith the patient's activity level and/or a change in activity level,then flow may return to receiving at 1010. If the change is notcommensurate with the patient's activity level or change in activitylevel, then one or more actions may be taken at 1070 or 1080, such asissuing a pathological state (e.g., an epileptic seizure) detection,issuing a warning of the pathological state, delivering a therapy forthe pathological state to the patient, or logging the pathological stateor the severity thereof. It may be the case that a pathological statedetected at 1070 (arising from a body signal value decrease notcommensurate with a change in the patient's activity level or a changethereof) may be different from one detected at 1080. In other words,decreases or increases in one or more of autonomic, metabolic,endocrine, or tissue stress signal values may be greater or lesser thanexpected from the patient's activity level, and a granularity of outputsbetween elements 1070 and 1080 may exist.

FIG. 11 shows a conceptual depiction of pathological andnon-pathological body data (e.g., heart rate) value ranges. Certainheart rate ranges, such as below 50 bpm and above 150 bpm, areessentially always pathological when seen in patients having normallevels of physical fitness and either resting or engaged in mildactivity (e.g., walking). Intermediate heart rate ranges, such as from50-150 bpm, may be pathological, or may be non-pathological, dependingon the kinetic and/or emotional/cognitive activity levels of thepatient. In other words, heart rate values that are non-pathological orphysiologic for certain activity levels may be indicative of apathological change (e.g. a seizure) for other activity levels.

FIG. 12 shows a flowchart representation of a method 1200, according tosome embodiments of the present disclosure. A body index range value isdetermined from patient data at 1210. If the body index range value isfound not to be ictal at 1220, flow returns to 1210. If the body indexrange value is found to be ictal at 1220, a determination is made at1230 whether the patient is undergoing activity. If the patient is notundergoing activity, the ictal body index range value is indicative of apathological state (e.g., a seizure), and a detection of thepathological state may be issued at 1250. If the patient is undergoingactivity, a determination may be made at 1240 whether the level of theactivity is commensurate with the activity. If it is not, then adetection of the pathological state may be issued at 1250. If it is,then flow returns to 1210.

The methods depicted in FIGS. 6-10 and 12 and described above may begoverned by instructions that are stored in a non-transitory computerreadable storage medium and that are executed by, e.g., a processor 217of the medical device 200. Each of the operations shown in FIGS. 6-10may correspond to instructions stored in a non-transitory computermemory or computer readable storage medium. In various embodiments, thenon-transitory computer readable storage medium includes a magnetic oroptical disk storage device, solid state storage devices such as flashmemory, or other non-volatile memory device or devices. The computerreadable instructions stored on the non-transitory computer readablestorage medium may be in source code, assembly language code, objectcode, or other instruction format that is interpreted and/or executableby one or more processors.

In certain embodiments, the present disclosure relates to a detection ofan undesirable (e.g., pathological) state change thorough thedetermination of changes (e.g., increases or decreases) in the values ofbody indices in relation to reference values regardless of whether ornot said reference value is pathological or non-pathological but takinginto account the work or activity level of the patient and, whereapplicable, environmental conditions. For example, in the case of apatient with an abnormally elevated heart rate, a decrease in said ratetoward or into the normal range may be indicative of a pathologicalstate such as an epileptic seizure that reduces heart rate.

In some embodiments, the present disclosure relates to the followingnumbered paragraph:

201. A non-transitory computer readable program storage unit encodedwith instructions that, when executed by a computer, perform a method ofdetecting a pathological body state of a patient, comprising:

determining an activity level of said patient; and

determining a non-pathological range for said body index, based at leastin part on said activity level.

301. A non-transitory computer readable program storage unit encodedwith instructions that, when executed by a computer, perform a method,comprising:

determining if a body index of a patient is outside a non-pathologicalrange;

determining if the patient's kinetic activity is commensurate with thebody index value;

indicating the occurrence of a seizure, if the kinetic activity is notcommensurate with the body index value.

401. A method for detecting a pathological body state of a patient,comprising:

receiving a first body signal of the patient;

determining a change in a first body index, based on said first bodysignal;

determining an activity level of said patient;

determining if said change in said first body index is commensurate withsaid determined activity level; and,

taking a further action in response to determining that said change insaid first body index is not appropriate/commensurate/expected/normalfor said determined activity level.

What is claimed:
 1. A method for detecting a pathological body state ofa patient, comprising: receiving a first body signal of the patient;determining a first body index from the first body signal; determiningan activity level of the patient; determining a non-pathological rangefor the first body index, based at least in part on the activity level;comparing the first body index to the non-pathological range for thefirst body index; detecting a pathological body state when the firstbody index is outside the non-pathological range.
 2. The method of claim1, further comprising determining at least a second body index;determining a non-pathological range for the second body index, based atleast in part on the activity level; comparing the second body index tothe non-pathological range for the second body index; and whereindetecting the pathological state comprises detecting the pathologicalstate when the first body index is outside the non-pathological rangefor the first body index and the second body index is outside thenon-pathological range for the second body index.
 3. The method of claim1, further comprising: in response to detecting the pathological state,performing at least one further action selected from issuing a notice ofthe detecting, delivering a therapy, issuing a warning, logging a timeof occurrence of the detecting, logging a response to a therapy, andlogging a severity of the pathological state.
 4. The method of claim 1,wherein the first body index is selected from heart rate, heart raterhythm, heart rate variability, blood pressure, respiratory rate,respiratory rhythm, tidal CO₂, kinetic activity, cognitive activity,dermal activity, arterial pH, cortisol level, catecholamine level, orblood oxygen saturation.
 5. The method of claim 1, wherein determiningthe activity level comprises analyzing a body signal of the patient,wherein the analyzing is performed on sensed data from one or more of anaccelerometer, an inclinometer, an electromyography (EMG) sensor, amuscle temperature sensor, an oxygen consumption sensor, a lactic acidaccumulation sensor, a sweat sensor, a neurogram sensor, a forcetransducer, or an ergometer.
 6. The method of claim 1, whereindetermining the non-pathological body index range is further based atleast in part on one or more of a time of day, an environmentalcondition, a patient's body weight and height, a patient's body massindex, a patient's gender, a patient's age, an indicator of thepatient's overall health, or an indicator of the patient's overallfitness.
 7. The method of claim 1, wherein the activity level is anactivity level for a time window.
 8. The method of claim 1, whereindetermining the activity level occurs in real time.
 9. The method ofclaim 1, wherein the pathological state is an epileptic event.
 10. Themethod of claim 1, further comprising repeating the steps of determiningan activity level of the patient and determining a non-pathologicalrange for the first body index at a time interval ranging from about 100times per second to about once every four hours.
 11. The method of claim1, wherein determining a non-pathological range for the first body indexcomprises determining the non-pathological range for the first bodyindex for a first time point based on the patient's activity in a firsttime window prior to the first time point.
 12. The non-transitorycomputer readable program storage unit of claim 12, wherein the durationof the first time window is from 1 second to 2 hours.
 13. The method ofclaim 1 wherein determining a first body index from the first bodysignal comprises determining a change in the first body index, andwherein detecting the pathological body state when the first body indexis outside the non-pathological range comprises determining if thechange in the first body index is commensurate with the determinedactivity level.
 14. A method of determining a pathological state in apatient, comprising: receiving data relating to an activity level of thepatient; determining an activity level of the patient based on the datarelating to an activity level; receiving at least one body signal of thepatient; determining at least a first body index based on the at leastone body signal; dynamically determining a reference value range for theat least a first body index based on the activity level; determiningthat the patient is in one of a non-pathological state and apathological state, wherein the patient is determined to be in anon-pathological state if the at least a first body index is within thereference value range for the activity level, and the patient isdetermined to be in a pathological state if the at least a first bodyindex is outside the reference value range; and taking at least onefurther action based on determining that the patient is in apathological state, wherein the further action is selected from treatingthe pathological state, issuing a warning to the patient or a caregiverregarding the pathological state, logging the occurrence of thepathological state, logging the response to a therapy, or logging aseverity of the pathological state.
 15. The method of claim 14, whereinthe reference value range comprises one of a non-pathological range anda pathological range.
 16. The method of claim 14, wherein thepathological state is an epileptic seizure.
 17. The method of claim 14,wherein the at least one body signal is selected from a cardiac signal,a respiratory signal, a blood signal, a dermal signal and an endocrinesignal.
 18. The method of claim 14, wherein the first body index isselected from: a cardiac index based on the cardiac signal, wherein thecardiac index is selected from a heart rate, heart rhythm, a heart ratevariability, and a blood pressure; a respiratory index based on therespiratory signal, wherein the respiratory index is selected from arespiratory rate, respiratory rhythm, blood oxygen saturation, and anend tidal CO₂ concentration; a dermal index based on the dermal signal,wherein the dermal index is selected from a skin resistivity and a skinconductivity; a blood index based on the blood signal, wherein the bloodindex is selected from an arterial pH and a lactic acid concentration;and an endocrine index based on the endocrine signal, wherein theendocrine signal is selected from a cortisol level and a catecholaminelevel.
 19. A medical device system, comprising: at least one kineticsensor, each the sensor configured to collect at least one kineticsignal from a patient; an activity level module configured to determinean activity level of the patient, based at least in part on the at leastone kinetic signal; at least one sensor configured to sense a bodysignal; a body index determination module configured to determine atleast a first body index based on the sensed body signal; a body indexrange module, configured to determine a non-pathological body indexrange for the at least a first body index, based at least in part on theactivity level; and a pathological state determination module,configured to determine that the patient is in one of a non-pathologicalstate and a pathological state, wherein the patient is determined to bein a non-pathological state if the at least a first body index is withinthe non-pathological body index range for the at least a first bodyindex, and the patient is determined to be in a pathological state ifthe at least a first body index is outside the non-pathological bodyindex range for the at least a first body index.
 20. The medical devicesystem of claim 19, wherein the body signal is selected from heart rate,heart rhythm heart rate variability, blood pressure, respiratory rate,respiratory rhythm, end tidal CO₂, dermal activity, arterial pH,cortisol level, catecholamine level, or blood oxygen saturation.